Economic Burden of Atopic Manifestations in Patients With Atopic Dermatitis - Analysis of Administrative Claims

BACKGROUND: Atopic dermatitis (AD) has been associated with atopic manifestations (AMs), such as food allergies, asthma, allergic rhinitis, and allergic conjunctivitis. OBJECTIVES: To (1) compare the risk of developing AMs in patients with AD versus those without AD, (2) estimate the incremental costs attributable to AMs in patients with AD, and (3) examine the factors associated with incremental costs. METHODS: In this retrospective cohort study, the authors used MarketScan research databases containing medical and pharmacy claims with dates of service from January 1, 1999, to December 31, 2004. Patients were considered to have AD if they had at least 1 medical claim with a primary or secondary diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 691.8x) or contact dermatitis or other eczema of unspecified cause (ICD-9-CM codes 692.9x). To create comparable study cohorts, patients with AD were matched with non-AD patients using propensity scores that represented the likelihood of developing AD as predicted by logistic regression. After propensity score matching, the AD and non-AD cohorts did not statistically differ with respect to age, gender, geographic region, type of health insurance, Charlson Comorbidity Index, or baseline measures of medical and prescription drug utilization. The relative risks of developing AMs in the AD and non-AD cohorts were estimated using competing risk-survival analysis. AM was defined by ICD-9-CM codes for asthma (493.xx), allergic rhinitis (477.xx), allergic conjunctivitis (372.05 or 372.14), and food allergy (693.1x, 692.5x, 995.60). The annual incremental cost attributable to AMs in these AD patients was calculated from medical claims with AM and AD diagnosis codes and from pharmacy claims for prescription drugs used to treat asthma, allergic rhinitis, allergic conjunctivitis, or food allergy, and 95% confidence intervals (CIs) were calculated using the bootstrap method. RESULTS: Patients with AD were significantly more likely to develop AMs than patients without AD (21.8% versus 16.9%, adjusted relative risk [RR]=1.33, 95% CI, 1.28-1.38). Among AD patients who developed AMs, allergic rhinitis was the most frequent manifestation (66.3%), followed by asthma (24.8%), allergic conjunctivitis (7.6%), and food allergy (1.8%). The incidence and adjusted RRs of developing AM for AD patients versus comparison patients were 5.3% versus 4.5% for asthma (RR=1.20, 95% CI, 1.12-1.29), 14.6% versus 11.2% for allergic rhinitis (RR=1.35, 95% CI, 1.29-1.41), 1.6% versus 1.1% for allergic conjunctivitis (RR=1.50, 95% CI, 1.31-1.72), and 0.3% versus 0.1% for food allergy (RR=2.35, 95% CI, 1.66-3.32). The annual AD + AM treatment costs for patients with AD increased substantially after they developed AMs. The additional financial burden attributable to AMs was estimated to be $482 per year, an almost 1.5-fold increase compared with AD cost alone (from $338 before AM development to $820 afterward, P less than 0.001), with approximately equal distribution of costs between medical services ($243) and prescription drugs ($239). The largest incremental costs were observed in asthma ($973), followed by allergic rhinitis ($341). CONCLUSIONS: Patients with AD are significantly more likely to develop AM compared with patients without AD. The total treatment costs for AD patients who developed AMs were nearly 2.5 times the total treatment costs for patients with AD alone.

A topic dermatitis (AD) is a common, pruritic, recurring inflammatory skin disease affecting 15% to 30% of children worldwide. [1][2][3][4][5][6][7] Although it is often viewed as a minor dermatological disorder, studies have shown that AD is a disease with substantial associated costs and morbidity. [8][9] In the United States, the cost of illness for AD borne by thirdparty payers ranged from $0.9 billion to $3.8 billion annually for privately insured and Medicaid patients under 65 years of age. 10 This disorder has increased in prevalence 2-to 3-fold since 1970. 3

Economic Burden of Atopic Manifestations in Patients With Atopic Dermatitis-Analysis of Administrative Claims
• Patients with atopic dermatitis (AD) are more likely than those without AD to present with atopic manifestations (AMs) such as asthma (odds ratio [OR] = 1.45-2.17), allergic conjunctivitis (OR = 2.10), allergic rhinitis (OR = 1.53-2.51), and food allergies (OR = 3.20-6.14); however, these figures represent concomitant associations, not assessments of AM emergence in patients who first developed AD.
• Compared with patients without a diagnosis code for AD on a medical claim, the relative risk (RR) of developing AM in patients with at least 1 medical claim with a diagnosis of AD was 1.20 for asthma, 1.35 for allergic rhinitis, 1.50 for allergic conjunctivitis, and 2.35 for food allergy, with an overall RR of 1.33 (95% CI, 1.28-1.38). • A subsequent diagnosis of AM in AD patients was associated with total medical costs that more than doubled in the subsequent 12 months ($820 per patient) compared with the 12 months preceding the AM diagnosis ($338 per patient), representing a $3.81 per member per year incremental cost due to AD across the entire enrollee population.

What this study adds
Note: An editorial on the subject of this article appears on pages 810-11 of this issue.
Alli dentifiedA Dp atientsh ad continuous health and prescription coverage from 12 months prior to thei ndex date througha tl east 24 months a fter thei ndexd atea nd were followed untilt he endo ft he studyp eriodo rl osso fc overage. AD patients whod eveloped AMsd uringt he follow-upp eriod were included in thea nalysiso fA M-relatedc ostso nlyi ft hey had( 1) at least1 2m onthso fe ligibility from thei ndexd ate (ADd iagnosis)t hrought he AM diagnosis date,a nd (2)a tl east 12 months of eligibility from theA Md iagnosis date untilt he endofthe studyperiodorlossofcoverage.
AD patients whod eveloped AMsa tl east 1y eara fter AD diagnosisw erei ncludedi nt he calculationo fi ncrementalc osts associated with AM.T oensurethatcost calculations were based on time periodso fe qual length,t he annual incrementalc ost attributable to AM wasc alculateda st he differenceb etween (1) AD-onlycostsinthe 12-month period before thedevelopment of AM and(2) AD+AMcostsinthe 12-month period afterdevelopment of AM.T hisa pproachw as tak en to minimize bias in cost estimationdue to variancesinpatient characteristics anddisease severities.

Limitations
Foremost among the study limitations is that establishing a causal relationship between AD and AM is not possible using administrative claims. At best, longitudinal analysis of administrative claims permits identification of a temporal relationship. While our methods identified newly diagnosed AD patients without an AM diagnosis based on the 12-month pre-index period (i.e., no AD or AM during the pre-index period), we cannot be certain that AD preceded AM because of a short 1-year pre-index period. Second, in the matching of AD patients with non-AD patients within stratified blocks, propensity scores were applied to control for various risk factors, but the results may be influenced by other variables not recorded in the data set, such as clinical severity of disease or laboratory test results. Third, there is a potential source of bias due to the possible misclassification of AD or AMs based on patients identified via ICD-9-CM codes on medical claims and from pharmacy claims data. We attempted to adjust for the differences between the AD and comparison cohorts to minimize bias, but the impact of differential or nonrandom misdiagnosis bias cannot be ruled out. Although the use of insurance claim databases offers many advantages over self-reported disease databases, misdiagnosis or under-diagnosis of AD may be unavoidable. 10 If random misclassification occurs between the AD and comparison cohorts, then the bias of the relative risk would be toward the null (i.e., 1.0). However, if the misclassification is not random, then the bias may inflate the relative risk. [45][46] Fourth, the prescription drug costs were calculated based on the dispensing of the medications approved by the U.S. Food and Drug Administration (FDA) for treatment of AD or AM, but we cannot ascertain whether the prescribed medication was indeed used for the FDA-approved indications.
Fifth, theincremental costsassessed in this studyrepresent direct medicalcostsand thereforeunderestimatethe totalcosts to thesociety becau se thetreatment cos ts were basedsolely on thea mounts actually paid by health insurancec ompanies to health care providers. We didnot includecostsassociatedwith self-treatment usingo ver-the-countero ra lternative remedies, burden on family members,a nd loss of productivity 9,47 ;t hus, cautioni sa dvised in generalizing thee stimated treatment costsf romt hiss tudy.As ixth limitationi st he calculationo f incrementaltreatment costsbased on ashort follow-upperiod of 1yearafter AM diagnosis. Nonetheless,thislimitationmay have minimale ffect on cost estimation because incremental costswerecalculatedasthe differenceincostsbeforeand after developingAMs in thesamep atient to minimize inter-patient variation.
Because AD createsa ne conomic burden to some patients, families,and society, educationalprogramsfor patients or families of children with moderate to severe AD as well as psychosocial supportfor parentscould decrease theirburdens through loweredt reatment costsa nd improved outcomes. 48 In addition, cost-effectiveness studieso nd ifferent treatmentr egimensc an be recommendedt od ecreaset he economic impact of AD on society.